A walk through Never Never Land

Your patient is a healthy woman who just turned 50. She eats right, exercises, doesn't smoke, and takes no regular medications. She goes for examinations regularly and without fear. She presents with a painful, coffeebean- sized new lump in her right axilla. Her mammogram report from only 3 months ago was unremarkable. Her clinical breast exam is normal, as is the balance of her examination. You prescribe antibiotics with close follow-up, thinking Painful is not cancer-but you recommend a sonogram. At the return visit, the lump appears to be resolving. The radiologist finds two swollen nodes and recommends more antibiotics and another sonogram in 3 weeks. When the two nodes have not resolved, the radiologist recommends needle-aspiration biopsy. You insist on open biopsy with exploration. After removing a single node that did not appear suspicious, the surgeon calls 4 days later and tells you the patient has metastatic cancer.

Now imagine the patient is your wife.

Thanksgiving eve 2005, my wife's surgeon called us with this horrific news. We scheduled an emergent repeat mammogram, which was also unremarkable for cancer. Mocking us was the caveat on the bottom of the report: "Approximately 10% of mammograms cannot detect breast cancer.?" The hunt for the primary tumor began.

MRI of Debbi's right breast showed a mass consistent with breast cancer and two additional suspicious nodes in her axilla. The CT/PET scan was confirmatory, and there was also a suspicious internal mammary node in her right chest wall. She had a right breast lumpectomy with axillary node dissection the Monday before Christmas. Her cancer was stage 3C, and my level of concern approached panic. The pathology report described a 40% estrogen-positive, progesteronenegative tumor that was HER2/neu-negative.

The National Cancer Institute lists the 5-year life expectancy for patients with stage 3C breast cancer as slightly less than 33%. Dose-dense chemotherapy-given every 2 rather than every 3 weeks-offers survival rates more than double those dated national averages. But when the patient is your wife, even one chance in three of dying is unacceptable.

Debbi's oncologist and I looked for better protocols, perhaps in ongoing clinical trials. We examined one developed in Europe that used drugs administered in a dose-intense fashion, with doses increased to 50% more than the amount traditionally given. This regimen has more profound side effects than dose-dense therapy but offered a 91% 4-year survival. We estimated that with radiation and adjuvant drugs, Debbi's cure rate would exceed 95%.

Deb's fitness helped her get through treatment. Her bone pain from Neulasta escalated with each treatment, but except when having chemotherapy, she never missed a day of work. Periodically, her white count dropped to 800 cells/�L and Purel became her best friend, but she never stopped forging ahead. She redefined the word strength. And once her white count returned to normal, she even participated in the birth of our first grandchild.

Advanced metastatic breast cancer is not rare in a 50-ish woman, but it's certainly unusual, even for Long Island. We discussed her BRCA status and elected to have genetic testing performed. Approximately 95% of women will be positive or negative for BRCA-1 or BRCA-2; only a small percentage are "indeterminate." These women are in a Never Never Land with genetic sequencing so rare that too few patients have been followed long enough for their genetic risk to be determined. I knew my wife was one-in-a-million. Now I had genetic proof, because she fell into this category. She elected to have her ovaries removed because of our inability to screen her adequately for ovarian cancer.

We are past the 1-year mark since Deb completed chemotherapy. She will undergo aggressive imaging tests annually. In the meantime, we both look forward to spending a long time with our first grandchild, Isabella.

I love practicing medicine as a PA. We have instant access to ongoing clinical trials through the Internet, and genomic information has allowed us to make informed choices and to tailor screening for patients at risk. Genomics especially has markedly changed the treatment of cancer, and in a way that Watson and Crick probably couldn't imagine. I attended Cold Spring Harbor High School on Long Island's North Shore, near the Cold Spring Harbor Laboratory where James Watson worked. He spoke at my high school National Honor Society induction in 1970. I didn't realize how prescient he was until I thought about his words that day while I researched treatments for my wife. We have entered the genomic age. Life-and medicine-will never be the same.

[Author Affiliation]

LAWRENCE M. HERMAN, MPA, PA-C

[Author Affiliation]

Larry Herman is Assistant Professor and Senior Clinical Coordinator, Department of Physician Assistant Studies, New York Institute of Technology, Old Westbury, NY, and a staff PA in a private family practice. He also chairs CSAC for AAPA. He is married to Debbi, his best friend and arguably the strongest woman in the world, and he is the grandfather of Isabella.